Cited 4 times since 2023 (1.9 per year) source: EuropePMC Nature communications, Volume 14, Issue 1, 1 1 2023, Pages 544 Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response. Dekkers KF, Slieker RC, Ioan-Facsinay A, van Iterson M, BIOS consortium, Ikram MA, van Greevenbroek MMJ, Veldink JH, Franke L, Boomsma DI, Slagboom PE, Jukema JW, Heijmans BT
Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease.
